Introduction: Glutaminyl cyclase (QC) enzymes catalyze the post-translational processing of several substrates with N-terminal glutamine or glutamate to form pyroglutamate (pE) residue. In addition to physiological functions, emerging evidence demonstrates that human QCs play a part in pathological processes in diverse diseases such as Alzheimer's disease (AD), inflammatory and cancer diseases.Areas covered: In recent years, efforts to effectively develop QC small-molecule inhibitors have been made and different chemical classes have been disclosed. This review summarizes the patents/applications regarding QC inhibitors released from 2004 (first patent) to now. The patents are mostly described in terms of chemical structures, biochemical/pharmacological activities, and potential clinical applications.Expert opinion: For more than 15 years of research, the knowledge on the QC activity domain has considerably increased and therapeutic potential of QC inhibitors has been explored. An important number of studies and patents have been published to expand the use of QC inhibitors. QC enzymes are pharmacologically interesting targets to be used as an AD-modifying therapy, or for other QC-associated disorder. Distinct classes of chemical scaffolds and potential clinical uses have been claimed by various organizations. For the coming years, there is much to experience in the QC field.
Keywords: Alzheimer’s disease (AD); cancer; glutaminyl cyclase (QC); glutaminyl cyclase isoform (isoQC); inflammation; pyroglutamate residue (pE); small-molecule inhibitors.